Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic erythematosus patients
ABSTRACT Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the change in CD4+CD25+FoxP3+ T regulatory (Treg) cells in response to treatment. Two females (JQ and SA) of 19 and 25 years of age, fulfilling the 1997 American College of Rheumatology (ACR) criteria for SLE were infused with autologous BM-derived MSCs. Disease activity indexes and immunological parameters were assessed at baseline, 1, 2, 7 and 14 weeks. Peripheral blood lymphocyte (PBL) subsets and Treg cells were quantitated by flow cytometry, and MSCs tested for in-vitro suppression of activation and proliferation of normal PBLs. No adverse effects or change in disease activity indexes were noted during 14 weeks of follow-up, although circulating Treg cells increased markedly. Patient MSCs effectively suppressed in-vitro PBL function. However, JQ developed overt renal disease 4 months after infusion. MSC infusion was without adverse effects, but did not modify initial disease activity in spite of increasing CD4+CD25+FoxP3+ cell counts. One patient subsequently had a renal flare. We speculate that the suppressive effects of MSC-induced Treg cells might be dependent on a more inflammatory milieu, becoming clinically evident in patients with higher degrees of disease activity.
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- "Today, it is well accepted that MSCs have important immunosuppressive properties over the entire immune system , mainly exerting their effects on T, B, NK, and dendritic cells  . This immunomodulatory capacity of MSCs has opened new therapeutic prospects in the management of proinflammatory and autoimmune pathologies   . The therapeutic potential of MSCs has been demonstrated in a variety of autoimmune disease models including graftversus-host disease (GVDH) , experimental autoimmune encephalomyelitis (EAE)  , collagen-induced arthritis "
ABSTRACT: The Silences of the Archives, the Reknown of the Story. The Martin Guerre affair has been told many times since Jean de Coras and Guillaume Lesueur published their stories in 1561. It is in many ways a perfect intrigue with uncanny resemblance, persuasive deception and a surprizing end when the two Martin stood face to face, memory to memory, before captivated judges and a guilty feeling Bertrande de Rols. The historian wanted to go beyond the known story in order to discover the world of the heroes. This research led to disappointments and surprizes as documents were discovered concerning the environment of Artigat’s inhabitants and bearing directly on the main characters thanks to notarial contracts. Along the way, study of the works of Coras and Lesueur took a new direction. Coming back to the affair a quarter century later did not result in finding new documents (some are perhaps still buried in Spanish archives), but by going back over her tracks, the historian could only be struck by the silences of the archives that refuse to reveal their secrets and, at the same time, by the possible openings they suggest, by the intuition that almost invisible threads link here and there characters and events.Stem cell International 01/2015; 2015:1-14. DOI:10.1155/2015/140170 · 2.81 Impact Factor
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- "Although MSCs from the SLE patients show immunosuppressive activity, they undergo senescence relatively faster than MSC from age matched healthy controls  . Autologous MSC therapy in two SLE patients was safe but did not reduce the disease activity . A direct link between the SLE and SNPs in genes of the inflammasomes has been demonstrated . "
ABSTRACT: The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs) make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS), linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs) in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs.11/2013; 2013:929842. DOI:10.1155/2013/929842
Conference Paper: High-speed systolic implementation of fast QR adaptive filters[Show abstract] [Hide abstract]
ABSTRACT: A rectangular systolic array of processing units is presented for implementation of the QR adaptive filter. This array requires approximately 8 N processing units to exactly solve the least-squares adaptive filtering problem using QR factorization. If a processing unit takes 50 ns to perform a task, the array can be implemented at an adaptive-filter input sampling rate of 20 MHz, with no loss in characteristic high performance (of least squares), numerical stability, or accuracy. This improves on widely used gradient methods for adaptive filtering, which must insert increasing amounts of performance-degrading delay into the adaptive updating when either the speed of implementation or number of taps increase. A discussion of the structure and interconnection of the processing units is included, as well as computer simulations that verify the stability and performance of the adaptive processing arrayAcoustics, Speech, and Signal Processing, 1988. ICASSP-88., 1988 International Conference on; 05/1988